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ABST RACT
Neutropenia, secondary to immune destruction or maturation arrest, is commonly described as an adverse hematological effect of beta-lactam antibiotics. A 29-year-old woman was being treated with piperacillin/tazobactam due to draining heel osteomyelitis.
Herein, we present a case of reversible neutropenia occurring on the 25th day of treatment. Neutropenia resolved six days after discontinuation of piperacillin/tazobactam. We think that patients receiving prolonged treatment with piperacillin/tazobactam should be followed cautiously for neutropenia.
Key words: Piperacillin, tazobactam, neutropenia, adverse effect Re ce ived: 15.11.2011 • Ac cep ted: 17.02.2012 • Published: 29.03.2012
ÖZET
İmmün yıkıma veya olgunlaşma durmasına sekonder nötropeni beta-laktam antibiyotiklerin yaygın tanımlanan yan etkisidir. Yirmi dokuz yaşında kadın, akıntılı topuk osteomiyeliti nedeniyle piperasilin/tazobaktam tedavisi alıyordu. Burada, tedavisinin 25.
gününde ortaya çıkan geri dönüşümlü nötropeni olgusunu sunuyoruz. Piperasilin/tazobaktam kesildikten altı gün sonra nötrope- ni düzeldi. Uzamış piperasilin/tazobaktam tedavisi alan hastaların nötropeni açısından dikkatle izlenmeleri gerektiğini düşünüyo- ruz.
Anahtar kelimeler: Piperasilin, tazobaktam, nötropeni, yan etki
Geliş Tarihi: 15.11.2011 • Kabul Ediliş Tarihi: 17.02.2012 • Yayınlanma Tarihi: 29.03.2012
Piperacillin/Tazobactam-Induced Neutropenia: A Case Report
Piperasilin/Tazobaktam Tarafından Uyarılmış Nötropeni: Bir Olgu Sunumu
URL: http://www.mjima.org/
OLGU SUNUMU l CASE REPORT
Hayati DEMİRASLAN1, Sibel GÜRBÜZ2, Zehra DOĞAN TOMUL2, İlhami ÇELİK2
1 Erciyes Üniversitesi Tıp Fakültesi, Enfeksiyon Hastalıkları ve Klinik Mikrobiyoloji Anabilim Dalı, Kayseri, Türkiye
2 SB Kayseri Eğitim ve Araştırma Hastanesi, Enfeksiyon Hastalıkları ve Klinik Mikrobiyoloji Kliniği, Kayseri, Türkiye
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INTRODUCTION
Piperacillin/tazobactam (PT) is a beta-lactamase inhibitor that is a semi-synthetic ureidopenicillin with broad spectrum. Bone marrow suppression is a recog- nized adverse drug reaction of beta-lactam antibio- tics[1]. A recent systematic review supported the assumption that piperacillin can also have such adver- se effects[2]. We report a case of reversible neutrope- nia associated with PT. This report reinforces previous suggestions that monitoring of hematological parame- ters is important in patients receiving prolonged treat- ment with PT.
CASE REPORT
We report herein the case of a 29-year-old woman with a history of paralysis of the lower extremities cau- sed by lumbar 1-2 compression fracture due to a traffic accident 10 years ago. Her right heel had been burned one year ago, after which a foul-smelling wound drai- nage developed. She was admitted due to the right heel osteomyelitis. Gram-negative rods and gram- positive cocci were seen on Gram staining of the wound drainage sample. PT (4.5 g q8h) was given to the patient. Complete blood count (CBC) at baseline showed: hemoglobin 9.4 g/dL, white blood cell (WBC) count 18.800/mm3 and platelet count 461.000/mm3. Levels of creatinine, serum aminotransaminases and lactate dehydrogenase were in normal limits, but the level of albumin was 3.3 g/dL. Aerobic wound culture was negative. Teicoplanin was added on the 10th day of antimicrobial therapy because of wound drainage.
On the 23rd day of antimicrobial therapy, the patient’s body temperature rose to 38.0°C. She complained of
periumbilical pain and cramping during PT infusion, and her samples were analyzed for the infectious sour- ce. The blood and wound culture were negative, urine sample was sterile, and chest radiograph was normal.
Meanwhile, the treatment remained unchanged; howe- ver, for two days, the patient’s temperature was incre- ased, at 38.9°C and 38.6°C. On the 25th day of antimic- robial therapy, the leukocyte count dropped to 1400/
mm3 (absolute neutrophil count was 100/mm3) and platelet count to 194.000/mm3, and hemoglobin level was 10.4 g/dL. Neither eosinophilia nor rashes were detected. Daily CBC count was performed to monitor the leukocyte count. The courses of leukocyte and neutrophil counts including the PT discontinuation day are shown in Figure 1; teicoplanin was carried over.
The patient’s fever resolved one day after PT was dis- continued, and the leukocyte and absolute neutrophil counts reverted to normal six days after discontinuati- on. On the 28th day of hospitalization, wound drainage had completely ceased and healing was observed; she was discharged on the 30th day of hospitalization.
DISCUSSION
There is some information in the literature about the toxicity of prolonged PT treatment for conditions such as bone-related infections and empyema[3,4]. In non-neutropenic fever studies, the occurrence of pipe- racillin-related neutropenia is rare (0.04%)[2]. A high incidence of antibiotic-induced neutropenia among patients receiving prolonged PT therapy for bone-rela- ted infections has been reported, with toxicity related to the cumulative dose. It was noticed that clinical fin- dings like fever and rash should be considered as
Figure 1.
The courses of leukocyte and neutrophil counts.
80007000 6000
leu/mm3 neu/mm3 50004000
30002000 1000
3 10 17 25 26 27
6700 4800
2500 6300
3500 3900
1400900
100 100 100 300 500 900 2100 4700 27003300 2500 2700
28 29 30 31 0
Day of withdrawal
of Pip/taz
days
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preceding signs of neutropenia[3]. Two days before the onset of neutropenia, the patient complained of fever and periumbilical pain, and although the periumbilical pain resolved, the patient’s fever persisted for two more days. Moreover, neutropenia appeared after the patient had received a mean of 26.8 days of therapy and a mean cumulative dose of 330.3 g of piperacil- lin[3]. Another report suggests that patients on a high cumulative dose of PT must be cautious of neutrope- nia[5]. In our patient, neutropenia occurred with a cumulative dose of 328.5 g PT on the 25th day. She had been receiving teicoplanin as well for 15 days when the neutropenia was discovered. To our knowled- ge, a case of leukopenia with neutropenia (WBCs 2000/mm3, neutrophils 46%) associated with teicopla- nin was reported after 20 days of teicoplanin administ- ration. Furthermore, after teicoplanin was discontinu- ed, WBCs and neutrophil counts normalized[6]. In another study, 95% of cases showed a recovery period of one to seven days after the withdrawal of beta-lac- tams[1]. Comparatively, neutrophil counts of our patient decreased to 100/mm3. However, neutropenia promptly reversed after discontinuation of PT, and teicoplanin was continued. After six days, neutrophil counts had completely recovered.
In conclusion, because the true incidence of adver- se effects is unknown, patients receiving prolonged PT treatment should be carefully followed for neutropenia.
Moreover, the fever could be an early sign requiring precise evaluation of PT-induced neutropenia.
RE FE REN CES
1. Neftel KA, Hauser SP, Muller MR. Inhibition of granulopo- iesis in vivo and in vitro by beta-lactam antibiotics. J Infect Dis 1985; 152: 90-8.
2. Scheetz MH, McKoy JM, Parada JP, Djulbegovic B, Raisch DW, Yarnold PR, Zagory J, Trifilio S, Jakiche R, Palella F, Kahn A, Chandler K, Bennett CL. Systematic review of piperacillin-induced neutropenia. Drug Saf 2007; 30: 295-306.
3. Peralta FG, Sanchez MB, Roiz MP, Pena MA, Tejero MA, Arjona R. Incidence of neutropenia during treatment of bone-related infections with piperacillin/tazobactam. Clin Infect Dis 2003; 37: 1568-72.
4. Ekmekci A, Yakar F, Tufan F, Demirturk M, Cagatay A.
Piperasilin/Tazobaktama bağlı kemik iliği baskılanması ile seyreden bir olgu sunumu. Nobel Med 2007; 4: 28-30.
5. Ruiz-Irastorza G, Barreiro G, Aguirre C. Reversible bone marrow depression by high-dose piperacillin/tazobactam.
Br J Haematol 1996; 95: 611-2.
6. Del Favero A, Patoia L, Bucaneve G, Biscarini L, Menichetti F. Leukopenia with neutropenia associated with teicoplanin therapy. Ann Pharmacother 2007; 41:
891-4.
Yazışma Adresi /Address for Correspondence Yrd. Doç. Dr. Hayati DEMİRASLAN Erciyes Üniversitesi Tıp Fakültesi Enfeksiyon Hastalıkları ve Klinik Mikrobiyoloji Anabilim Dalı Kayseri-Türkiye E-posta: [email protected]
